Identification of Gravida Serum Biomarkers for Noninvasive Prenatal Diagnosis Fetal Congenital Heart Disease

Xia, Yi; Cheng, Lin; Duan, Jie; Ma, Jun; Zhang, Yuanzhen

doi:10.1007/s12265-022-10301-5

Cited by 2 publications

(2 citation statements)

References 27 publications

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“…However, due to the lack of clinical data, further research is needed to explore its potential as a new cardiac biomarker [ 12 ]. Nonetheless, our findings not only further support the potential of POSTN as a new cardiac disease biomarker but also validate the reliability of our previous proteomic results [ 10 ].…”

Section: Discussionsupporting

confidence: 90%

The comprehensive study on the role of POSTN in fetal congenital heart disease and clinical applications

Xia,

Chen,

et al. 2023

J Transl Med

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Background Congenital heart defect (CHD) is the most common congenital abnormality, and it has long been a clinical and public health concern. Our previous findings have found Periostin (POSTN) and Pappalysin-1 (PAPPA) as potential biomarkers for fetal CHD. We aim to further elucidate POSTN's role in fetal heart development and explore the clinical applicability of POSTN and PAPPA as diagnostic marker for fetal CHD. This study is poised to establish a theoretical framework for mitigating the incidence of CHD and advance a novel approach for prenatal screening of fetal CHD. Methods We verified differential expression of POSTN and PAPPA in gravida serum and fetal amniotic fluid based on our previous research. We established the Postn knockout mouse by CRISPR/Cas9 to investigate whether Postn deletion leads to cardiac abnormalities in mice. Besides, we explored the mechanism of POSTN on heart development through Postn knockout mouse model and cell experiments. Finally, we established the logistic regression model and decision curve analysis to evaluate the clinical utility of POSTN and PAPPA in fetal CHD. Results We observed a significant decrease in POSTN and increase in PAPPA in the CHD group. Atrial septal defects occurred in Postn−/− and Postn± C57BL/6 fetal heart, while ventricular septal defects with aortic saddle were observed in Postn± C57BL/6 fetal heart. Disruption of the extracellular matrix (ECM) in cardiomyocytes and multiple abnormalities in cellular sub-organelles were observed in Postn knockout mice. POSTN may positively regulate cell behaviors and unsettle ECM via the TGFβ-Smad2/3 signaling pathway. The combination of serum biomarkers POSTN and PAPPA with Echocardiogram can enhance the diagnostic accuracy of CHD. Furthermore, the comprehensive model including POSTN, PAPPA, and two clinical indicators (NT and age) exhibits significantly higher predictive ability than the diagnosis group without the use of serum biomarkers or clinical indicators. Conclusions It is the first evidence that Postn deletion leads to cardiac developmental abnormalities in fetal mice. This may involve the regulation of the TGFβ signaling pathway. Importantly, POSTN and PAPPA possess clinical utility as noninvasive prenatal promising screening indicators of CHD.

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Section: Discussionsupporting

confidence: 90%

The comprehensive study on the role of POSTN in fetal congenital heart disease and clinical applications

Xia,

Chen,

et al. 2023

J Transl Med

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“…It belongs to the family of IFN-induced proteins that have a wide range of antiviral functions and have been studied mainly in RNA viruses [4]. POSTN encodes a secreted extracellular matrix protein that functions in tissue development and regeneration, including wound healing, and ventricular remodeling following myocardial infarction [33]. THBS1 encodes an adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions.…”

Section: Discussionmentioning

confidence: 99%

The Communal Pathogenesis, Autophagy Mechanism and Potential Therapeutic Targets in Dilated Cardiomyopathy and Viral Myocarditis

Zhu

Cao

et al. 2022

Preprint

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Background: Viral myocarditis (VMC) is an important factor leading to dilated cardiomyopathy (DCM), yet the molecular mechanism is far from elucidated. Autophagy has been proven to be associated with cardiomyopathies, but the role of autophagy in the progression from VMC to DCM is unclear and requires further study. Methods: Common differentially expressed genes (CoDEGs) in DCM and VMC were screened from the related microarray datasets. Enrichment analysis and protein-protein interaction analysis were performed to identify key pathways and Hub Genes. The differentially expressed ARGs were used for receiver operating characteristic analysis to identify potential biomarkers. The expression of these identified genes was further verified in external datasets. Results: A total of 134 CoDEGs were identified and these genes were mainly enriched in the pathways of “inflammatory response”, “response to virus”, “JAK-STAT signaling pathway”, and “PI3K-Akt signaling pathway”. The top 6 hub genes CCND1, STAT3, THBS1, CCL2, POSTN, IFIT2 and 11 Common differentially expressed ARGs BCL2L1, CCL2, CCND1, NAMPT, NRG1, S100A8, S100A9, SESN3, SNCA, STAT3, TUBA1C were identified. These genes had a similar expression pattern in DCM and VMC. Finally, in the external validation dataset, mice showed an enhanced inflammatory response and apoptotic response at the initial stage of coxsackievirus B3 infection and indicated DCM phenotype in the chronic stage of infection. Conclusions: Inflammatory response and autophagy may be the vital biological pathways in the progression from VMC to DCM, and appropriate intervention of these processes may be a novel and potential therapeutic strategy.

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Identification of Gravida Serum Biomarkers for Noninvasive Prenatal Diagnosis Fetal Congenital Heart Disease

Cited by 2 publications

References 27 publications

The comprehensive study on the role of POSTN in fetal congenital heart disease and clinical applications

The comprehensive study on the role of POSTN in fetal congenital heart disease and clinical applications

The Communal Pathogenesis, Autophagy Mechanism and Potential Therapeutic Targets in Dilated Cardiomyopathy and Viral Myocarditis

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